Accurate Detection of Dysmorphic Nuclei Using Dynamic Programming and Supervised Classification

PLoS One. 2017 Jan 26;12(1):e0170688. doi: 10.1371/journal.pone.0170688. eCollection 2017.

Abstract

A vast array of pathologies is typified by the presence of nuclei with an abnormal morphology. Dysmorphic nuclear phenotypes feature dramatic size changes or foldings, but also entail much subtler deviations such as nuclear protrusions called blebs. Due to their unpredictable size, shape and intensity, dysmorphic nuclei are often not accurately detected in standard image analysis routines. To enable accurate detection of dysmorphic nuclei in confocal and widefield fluorescence microscopy images, we have developed an automated segmentation algorithm, called Blebbed Nuclei Detector (BleND), which relies on two-pass thresholding for initial nuclear contour detection, and an optimal path finding algorithm, based on dynamic programming, for refining these contours. Using a robust error metric, we show that our method matches manual segmentation in terms of precision and outperforms state-of-the-art nuclear segmentation methods. Its high performance allowed for building and integrating a robust classifier that recognizes dysmorphic nuclei with an accuracy above 95%. The combined segmentation-classification routine is bound to facilitate nucleus-based diagnostics and enable real-time recognition of dysmorphic nuclei in intelligent microscopy workflows.

MeSH terms

  • Algorithms
  • Animals
  • Benchmarking
  • Cell Nucleus / classification
  • Cell Nucleus / pathology
  • Cell Nucleus / ultrastructure*
  • Dermis / pathology
  • Dermis / ultrastructure
  • Fibroblasts / pathology
  • Fibroblasts / ultrastructure*
  • Fibrosarcoma / diagnosis
  • Fibrosarcoma / pathology
  • Fibrosarcoma / ultrastructure*
  • Growth Disorders / diagnosis
  • Growth Disorders / pathology
  • Humans
  • Image Processing, Computer-Assisted / methods
  • Image Processing, Computer-Assisted / statistics & numerical data*
  • Mice
  • Microscopy, Fluorescence / methods
  • Microscopy, Fluorescence / statistics & numerical data*
  • Neurons / pathology
  • Neurons / ultrastructure
  • Pattern Recognition, Automated / statistics & numerical data*
  • Primary Cell Culture
  • Progeria / diagnosis
  • Progeria / pathology

Supplementary concepts

  • Progeroid Syndrome, Congenital, Petty Type

Grants and funding

This work was supported by the Flemish Institute for Scientific Research (FWO PhD Fellowship awarded to MV, Grant N°: 11ZF116N; www.fwo.be) and the University of Antwerp (awarded to WDV, Grant BOF/29267 and BOF/30112; www.uantwerpen.be). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.